Previous GeneCards Identifiers for PRKAG2 Gene

Summaries for PRKAG2 Gene

Entrez Gene Summary for PRKAG2 Gene

AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic alpha subunit, a noncatalytic beta subunit, and a noncatalytic regulatory gamma subunit. Various forms of each of these subunits exist, encoded by different genes. AMPK is an important energy-sensing enzyme that monitors cellular energy status and functions by inactivating key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This gene is a member of the AMPK gamma subunit family. Mutations in this gene have been associated with Wolff-Parkinson-White syndrome, familial hypertrophic cardiomyopathy, and glycogen storage disease of the heart. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jan 2015]

Suggested Antigen Peptide Sequences for PRKAG2 Gene

Graphical View of Domain Structure for InterPro Entry

UniProtKB/Swiss-Prot:

The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1.

Belongs to the 5-AMP-activated protein kinase gamma subunit family.

Domain:

The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1.

The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2- and 3-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.

UniProtKB/Swiss-Prot

Cardiomyopathy, familial hypertrophic 6 (CMH6) [MIM:600858]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. CMH6 patients present Wolff-Parkinson-White ventricular preexcitation, enlarged myocytes without myofiber disarray, and glycogen-containing cytosolic vacuoles within cardiomyocytes. {ECO:0000269 PubMed:11371514, ECO:0000269 PubMed:11827995}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Glycogen storage disease of heart lethal congenital (GSDH) [MIM:261740]: Rare disease which leads to death within a few weeks to a few months after birth, through heart failure and respiratory compromise. {ECO:0000269 PubMed:15877279}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Wolff-Parkinson-White syndrome (WPWS) [MIM:194200]: A supernormal conduction disorder characterized by the presence of one or several accessory atrioventricular connections, which can lead to episodes of sporadic tachycardia. {ECO:0000269 PubMed:11407343, ECO:0000269 PubMed:11748095, ECO:0000269 PubMed:14722619}. Note=The disease is caused by mutations affecting the gene represented in this entry.